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Biomedical subjects

H J Shin

Publications and source records attributed to H J Shin.

At least 73 records · Page 4Linked to original sources
PubMed1999

Copper(II)-induced self-oligomerization of alpha-synuclein.

alpha-Synuclein is a component of the abnormal protein depositions in senile plaques and Lewy bodies of Alzheimer's disease (AD) and Parkinson's disease respectively. The protein was suggested to provide a possible nucleation centre for plaque formation in AD via selective interaction with amyloid beta/A4 protein (Abeta). We have shown previously that alpha-synuclein has experienced self-oligomerization when Abeta25-35 was present in an orientation-specific manner in the sequence. Here we examine this biochemically specific self-oligomerization with the use of various metals. Strikingly, copper(II) was the most effective metal ion affecting alpha-synuclein to form self-oligomers in the presence of coupling reagents such as dicyclohexylcarbodi-imide or N-(ethoxycarbonyl)-2-ethoxy-1,2-dihydroquinoline. The size distribution of the oligomers indicated that monomeric alpha-synuclein was oligomerized sequentially. The copper-induced oligomerization was shown to be suppressed as the acidic C-terminus of alpha-synuclein was truncated by treatment with endoproteinase Asp-N. In contrast, the Abeta25-35-induced oligomerizations of the intact and truncated forms of alpha-synuclein were not affected. This clearly indicated that the copper-induced oligomerization was dependent on the acidic C-terminal region and that its underlying biochemical mechanism was distinct from that of the Abeta25-35-induced oligomerization. Although the physiological or pathological relevance of the oligomerization remains currently elusive, the common outcome of alpha-synuclein on treatment with copper or Abeta25-35 might be useful in understanding neurodegenerative disorders in molecular terms. In addition, abnormal copper homoeostasis could be considered as one of the risk factors for the development of disorders such as AD or Parkinson's disease.

Alzheimer Disease↗
PubMed1999

Role of tryptophanyl residues in tobacco acetolactate synthase.

Acetolactate synthase (ALS) catalyzes the first common step in the biosynthesis of valine, leucine, and isoleucine. ALS is the target of three classes of herbicides, the sulfonylureas, the imidazolinones, and the triazolopyrimidines. Five mutants (W266F, W439F, W490F, W503F, and W573F) of the ALS gene from Nicotiana tabacum were constructed and expressed in Escherichia coli, and the enzymes were purified. The W490F mutation abolished the binding affinity for cofactor FAD and inactivated the enzyme. The replacement of Trp573 by Phe yielded a mutant ALS resistant to the three classes of herbicides. The other three mutations, W266F, W439F, and W503F, did not significantly affect the enzymatic properties and the sensitivity to the herbicides. These results indicate that the Trp490 residue is essential for the binding of FAD and that Trp573 is located at the herbicide binding site. The data also suggest that the three classes of herbicides bind ALS competitively.

Acetolactate Synthase↗
PubMed1999

Cytologic features of lymphoepithelial cyst of the pancreas: two preoperatively diagnosed cases based on fine-needle aspiration.

We describe the cytologic features seen in fine-needle aspiration (FNA) specimens from two cases of preoperatively diagnosed lymphoepithelial cyst (LEC) of the pancreas. Pancreatic LEC is a rare, true cyst of uncertain histogenesis that may clinically and radiologically mimic a pseudocyst or cystic neoplasm. Both our patients were middle-aged men who presented with vague abdominal pain. Computed tomography (CT) of the abdomen revealed a mass in or around the pancreas, and CT-guided percutaneous FNA (patient 1) and endoscopic ultrasound-guided FNA (patient 2) yielded paste-like yellow-gray material. Cytologic smears showed numerous anucleated squamous cells in a background of keratinous and amorphous debris. A few benign nucleated squamous cells and plate-like cholesterol crystals were also seen. Unlike LEC of the head and neck region, only rare lymphocytes and histiocytes were present. Pancreatic LEC was diagnosed based on these cytologic findings and was histologically confirmed following cyst enucleation (patient 1) and partial pancreatectomy (patient 2). We conclude that preoperative FNA and recognition of the characteristic cytologic pattern will enable conservative surgical management of pancreatic LEC. Diagn. Cytopathol. 1999;21:346-350.

Biopsy, Needle↗
PubMed1999

MRI of primary meningeal tumours in children.

Childhood meningeal tumours are uncommon and mostly meningiomas. We reviewed the histological and radiological findings in meningeal tumours in six children aged 12 years or less (four benign meningiomas, one malignant meningioma and one haemangiopericytoma). Compared to the adult counterpart, childhood meningiomas showed atypical features: cysts, haemorrhage, aggressiveness and unusual location. MRI features varied according to the site of the tumour, histology, haemorrhage, and presence of intra- or peritumoral cysts. Diagnosis of the extra-axial tumour was relatively easy in two patients with meningiomas, one malignant meningioma and one haemangiopericytoma. MRI findings strongly suggested an intra-axial tumour in two patients with benign meningiomas, because of severe adjacent edema. Awareness of the variable findings of childhood meningiomas and similar tumours may help in differentiation from brain tumours.

Brain↗
PubMed1999

Treatment of intracranial nongerminomatous malignant germ cell tumor in children: the role of each treatment modality.

To investigate the role of surgical tumor resection, radiotherapy and chemotherapy, the outcome of treatment in 17 children with nongerminomatous malignant germ cell tumor (NG-MGCT) was reviewed. The median follow-up period was 38 months after diagnosis, and the overall 3-year survival rate was 75%. Eleven patients who underwent craniospinal radiation (CSRT) did not receive chemotherapy. In 4 of them more than 90% of the tumor was removed, and they were free of disease at 16, 30, 93 and 111 months after surgery. Among the other 7, who did not undergo tumor resection (n=5) or had considerable residual tumor (n=2), 2 were disease-free at 73 and 88 months after diagnosis, and 5 died of recurrences. Of 6 patients who received cisplatin and etoposide chemotherapy in addition to CSRT, none showed intracranial recurrence, regardless of the extent of removal. The authors believe that multimodal treatment is the preferred choice and that chemotherapy plays an important role, especially when a significant amount of tumor remains after surgery. CSRT plays a major role at least in some patients. If chemotherapy is not feasible, radical removal plus CSRT seems to be an alternative.

Adolescent↗
PubMed1999

Purification and characterization of N-Acetylglucosamine 6-phosphate deacetylase from Thermus caldophilus.

N-Acetylglucosamine 6-phosphate deacetylase [EC 3.5.1.25] was purified and biochemically characterized from an extreme thermophile, Thermus caldophilus GK24. The optimum temperature and pH of the enzyme were 80 degrees C and 7.5, respectively. The enzyme is a tetramer composed of identical 45 kDa subunits. The N-terminal amino acid sequence of the purified enzyme was determined to be MSVDLKTLHRRHVLTP. It hydrolyzed GlcNAc-6-P, but not GlcNAc-1-P or chitin oligosaccharides. The deacetylase activity was completely inhibited by the addition of 1 mM Cu2+, but moderately activated by that of 1 mM Mn2+ and Co2+. Within 2 h of reaction, 2 mM GlcNAc-6-P was completely hydrolyzed to GlcN-6-P and acetate by the action of the deacetylase.

Journal Article↗
PubMed1999

Pathogenicity of Korean isolates of Acanthamoeba by observing the experimental infection and zymodemes of five isoenzymes.

To determine the pathogenicity of Acanthamoeba spp. isolated in Korea and to develop a isoenzymatic maker, the mortality rate of infected mice, in vitro cytotoxicity against target cells and isoenzyme band patterns were observed. Five isolates of Acanthamoeba spp. (YM-2, YM-3, YM-4, YM-5, and YM-7) were used in this study as well as three reference Acanthamoeba spp. (A. culbertsoni, A. hatchetti, and A. royreba). According to the mortality rate of infected mice, Korean isolates could be categorized into three groups high virulent (YM-4), low virulent (YM-2, YM-5, YM-7) and the nonpathogenic group (YM-3). In addition, the virulence of Acanthamoeba spp. was enhanced by brain passage in mice. In the cytotoxicity assay against chinese hamster ovary cells, especially, the cytotoxicity of brain-passaged amoebae was relatively higher than the long-term cultivated ones. The zymodeme patterns of glucose-6-phosphate dehydrogenase (G6PD), malate dehydrogenase (MDH), hexokinase (HK), glutamate oxaloacetate transaminase (GOT) and malic enzyme (ME) of Acanthamoeba spp. were different among each isolate, and also between long-term cultured amoebae and brain passaged ones. In spite of the polymorphic zymodemes, a slow band of G6PD and HK, and an intermediate band of MDH were only observed in pathogenic Acanthamoeba spp., which should be used as isoenzymatic makers.

Acanthamoeba↗
PubMed1999

Isoenzyme patterns and phylogenetic relationships in Acanthamoeba spp. isolated from contact lens containers in Korea.

In order to refer to the basic information regarding the identification of isolates obtained from a contact lens container in Korea, the isoelectric focusing gel electrophoresis was employed to compare the isoenzyme band patterns among Acanthamoeba spp. including eight isolates and the simple pairwise dissimilarity analysis was carried out. For an alkaline phosphate development, isolate 7 and Acanthamoeba polyphaga showed homologous band patterns, and isolates 1, 2, and 3 showed the same patterns. For lactate dehydrogenase, similar patterns were observed in isolates 2 and 3. Isolates 3 and 5 showed homologous band patterns for malate dehydrogenase and glucose phosphate isomerase. For hexokinase, isolates 4, 7, and A, hatchetti showed the same band patterns. In others, a considerable number of interstrain polymorphisms was observed in nine isoenzyme band patterns. In Acanthamoeba group II, genetic distances among isolates 1, 2, 3, 4, and 5 ranged from 0.104 to 0.200. In comparison to A. castellanii, A. hatchetti, and A. polyphaga, genetic distances of isolates 7 and 8 were 0.254 and 0.219, respectively. In Acanthamoeba group III, including A. culbertsoni, A. healyi, and A. royreba, isolate 6 had genetic distances which ranged from 0.314 to 0.336. Finally, when comparing to the six reference Acanthamoeba, it was possible to classify isolates 1, 2, 3, 4, and 5, as genetically close-related species and as independent species group. Furthermore, isolates 6, 7 and 8 were identified as independent species as well.

Acanthamoeba↗
PubMed1999

Biochemical characterization of a UDP-sugar pyrophosphorylase from Thermus caldophilus GK24.

An extremely thermostable UDP-GlcNAc pyrophosphorylase has been purified from Thermus caldophilus GK24 by chromatographic methods including ion-exchange, hydrophobic interaction, and affinity chromatographies. The specific activity of the enzyme was enriched 41.8-fold, with a recovery of 2%. The molecular mass of the enzyme was 41 kDa by SDS/PAGE and 45 kDa by gel-filtration chromatography. The activity was maximum at 86 degrees C and its half-life at 95 degrees C was 30 min. Its optimum pH was 6.9 in the presence of Mg2+ ions. A biochemical study showed that UDP-GlcNAc pyrophosphorylase activity could be enhanced by fructose 1-phosphate, a precursor of UDP-GlcNAc. The enzyme showed a broad substrate specificity with sugar 1-phosphates, including glucose 1-phosphate, GlcNAc-1-P and xylose 1-phosphate. The enzyme was therefore named UDP-sugar pyrophosphorylase. The N-terminal and internal peptide sequences were determined and compared with known sequences from various sources. It was found that N-terminal sequence is similar to that of UDP-GlcNAc and UDP-glucose pyrophosphorylases from other bacterial sources.

Amino Acid Sequence↗
PubMed1998

A multidisciplinary approach to therapy for unresectable malignant thymoma.

BACKGROUND: The therapeutic outcome for unresectable, locally advanced, malignant thymoma has been poor. OBJECTIVE: To improve tumor resectability and patient survival rates by studying a multimodal approach to therapy for unresectable malignant thymoma. DESIGN: Prospective cohort study. SETTING: Tertiary care cancer center. PARTICIPANTS: All eligible patients had newly diagnosed, histologically proven, unresectable malignant thymoma. INTERVENTION: The treatment regimen consisted of induction chemotherapy (three courses of cyclophosphamide, doxorubicin, cisplatin, and prednisone), surgical resection, postoperative radiation therapy, and consolidation chemotherapy (three courses of cyclophosphamide, doxorubicin, cisplatin, and prednisone). Tissue samples were taken at the time of surgical resection for assessment of tumor necrosis and Ki-67 expression. MEASUREMENTS: Tumor response and resectability (both overall and after induction chemotherapy) and disease-free survival rate in patients who received multimodal therapy. RESULTS: 13 patients were consecutively enrolled from February 1990 to December 1996, and 12 evaluable patients were assessed for response. Disease responded to induction chemotherapy completely in 3 patients (25%) and partially in 8 patients (67%); 1 patient had a minor response (8%). Eleven patients had surgical resection; 1 refused surgery. Tumors were removed completely in 9 (82%) and incompletely in 2 (18%) of 11 patients who had been receiving radiation therapy and consolidation chemotherapy. All 12 patients are alive (100% at 7 years), with a median follow-up of 43 months, and 10 patients are disease free (73% disease-free survival at 7 years). A high correlation was seen between tumor necrosis after induction chemotherapy and Ki-67 expression (r=-0.88). CONCLUSIONS: Aggressive multimodal treatment is highly effective and may cure locally advanced, unresectable malignant thymoma.

Adult↗
PubMed1998

Metastatic small-cell carcinoma of the prostate diagnosed by fine-needle aspiration biopsy.

Fourteen fine-needle aspiration biopsies (FNABs) of metastatic small-cell carcinoma done on 12 patients who had histologically documented primary small-cell carcinoma of the prostate are described. The FNABs were of lymph node (four cases), liver (four cases), bone (two cases), pancreas (one case), perirectal soft tissue (one case), perineum (one case), and lung (one case). One patient underwent three FNABs. No patient had a second primary tumor elsewhere. Cytologic smears were cellular with numerous single tumor cells, many apoptotic bodies, and variable numbers of mitotic figures. Tight cell clusters with molded nuclei and finely stippled chromatin were seen in all cases. An organoid pattern of tumor cells was seen focally in two cases. Features distinguishing small-cell carcinoma from poorly differentiated prostate carcinoma were cell size, finely stippled chromatin, inconspicuous nucleoli, and numerous single tumor cells. Distinction from small-cell carcinoma of other primary sites requires clinical and radiologic correlation. We conclude that cytologic specimens are useful for documenting metastatic small-cell carcinoma of the prostate and for differentiating between it and conventional prostate carcinoma in metastatic sites.

Aged↗
PubMed1998

Is a diagnosis of infiltrating versus in situ ductal carcinoma of the breast possible in fine-needle aspiration specimens?

BACKGROUND: With widespread use of mammographic screening, more cases of ductal carcinoma in situ (DCIS) are being detected. Fine-needle aspiration (FNA) is an established and reliable method for diagnosing breast carcinoma. However, its usefulness in distinguishing infiltrating ductal carcinoma (IDC) from DCIS is controversial. METHODS: The authors retrospectively reviewed 36 breast FNAs (23 palpable lesions and 13 nonpalpable lesions) that were confirmed histologically as being exclusively DCIS. On review, 27 cases (75%) were categorized as carcinomas, and 9 cases (25%) were categorized as proliferative lesions with atypia. Findings of only these 27 carcinomas were compared with findings of 42 breast FNAs that surgically were proven to be IDC (> or = 85% invasive). Five key cytologic features compared included the presence of fibroadipose tissue, stromal fragments, benign epithelial groups, angulated tumor cell clusters, and tubular structures of tumor cells; for the first three features, the proximity with tumor cells also was noted. RESULTS: The presence of stromal fragments associated with tumor cells was significantly different between cases of DCIS (9 of 27; 33%) and IDC (29 of 42; 69%) (P = 0.006). Tubular structures were present only in IDCs (10 of 42; 24%) (P = 0.02). Nine of ten IDCs that had tubular structures also contained stromal fragments. No other cytologic features were different statistically between IDC and DCIS on FNA specimens. CONCLUSIONS: Tubular structures of tumor cells and the presence of stromal fragments in breast FNA are significant indicators of stromal invasion. However, the low occurrence rate of tubular structures (24% in this series) in IDC and the low specificity of stromal fragments limit their utility in separating IDC from DCIS. Nonetheless, if present, tubular structures in conjunction with stromal fragments can be used to evaluate stromal invasion in patients whose disease is being managed surgically.

Biopsy, Needle↗
PubMed1998

Optical design of the U7 undulator beamline at the Pohang Light Source.

The first insertion-device beamline at the Pohang Light Source is designed for high-resolution spectroscopy and spectromicroscopy. The beamline will contain a variable-included-angle plane-grating monochromator (VIA-PGM) using a grating substrate which has seven different grooves with different depths. The advantages of this scheme will be the fixed exit-slit position and the mechanical stability of the grating scan mechanism while changing the photon energy range. The beamline is designed to cover the photon energy range 20-2000 eV. The estimated spectral resolution, E/DeltaE, is above 8000 in the photon energy range below 500 eV, and above 4000 for the remaining photon energy range. The estimated flux at the end-station is of the order of 10(12) photons s(-1) (0.1% bandwidth)(-1).

Journal Article↗
PubMed1998

Fine-needle aspiration biopsy of metastatic small cell carcinoma from extrapulmonary sites.

Like a pulmonary counterpart, extrapulmonary small cell carcinoma (SCC) is an aggressive tumor with a high rate of metastasis. Forty-nine fine-needle aspiration biopsies (FNABs) (36 patients) of various primary sites other than the lung diagnosed as metastatic SCC (including Merkel cell carcinoma) were reviewed. FNABs were derived from lymph nodes (20), liver (7), bone (2), breast (1), pancreas (1), and skin/soft tissue (18). Primary tumor sites included the prostate (14), skin (11; Merkel cell carcinoma), cervix (5), urinary bladder (3), urethra (1), ovary (1), and parotid (1). Aspirates revealed predominantly dispersed single tumor cells with occasional clustering. Tumor cells were small with scant cytoplasm, fine powdery chromatin, and inconspicuous nucleoli. Nuclear molding, mitotic figures, and apoptotic bodies were frequently observed. In four cases, findings from the FNABs were used to render the initial diagnosis of SCC. FNAB is useful for determining whether metastases contain a SCC component, a finding that may alter clinical management. Cytologically, SCC from different primary sites cannot be differentiated, and its distinction requires clinical and radiographic correlation.

Adult↗
PubMed1998

Cerebrovascular effects of the bradykinin analog RMP-7 in normal and irradiated dog brain.

The effects of an intravenous (i.v.) injection of the bradykinin analog RMP-7 (100 ng/kg) were assessed in normal dogs and dogs with focal, radiation-induced brain lesions. A dose of 20 Gy was delivered to a point 0.75 cm from a removable interstitial 125I source; parameters relating to blood flow and permeability were quantified using computed tomography 2-8 weeks after irradiation. Blood flow-related endpoints included regional cerebral blood flow (rCBF), mean transit time of blood and vascular volume, while endpoints related to permeability included blood-to-brain transfer constant (Ki), brain-to-blood transfer constant and plasma volume. In unirradiated brain, an i.v. bolus of RMP-7 administered through the left cephalic vein induced a rapid and transient hypotension and a statistically significant increase in vascular volume; no alterations in any parameter related to permeability were observed. After irradiation, changes in rCBF after RMP-7 depended upon time after exposure, effects presumably due to changing morphology in the irradiated tissues. In the radiation lesions, significant increases in Ki were observed 5 minutes after injection of RMP-7, but those increases were not related to time after irradiation or alteration in blood flow-related parameters. Our results showed that RMP-7 selectively increased permeability in already damaged vasculature without affecting the extent or volume of radiation-induced vasogenic edema. These data suggest that RMP-7 may provide an effective means to enhance the delivery of compounds to an already compromised brain while not exacerbating the potential adverse effects of pre-existing vasogenic edema.

Animals↗
PubMed1998

Comparisons of the NACP self-oligomerizations induced by Abeta25-35 in the presence of dicyclohexylcarbodiimide and N-(ethoxycarbonyl)-2-ethoxy-1,2-dihydroquinoline.

NACP, the precursor protein of the non-amyloid beta/A4 protein (Abeta) component of Alzheimer's disease (AD) amyloid, also known as alpha-synuclein was shown to undergo self-oligomerization only in the presence of a modified Abeta fragment (residues 25 35) by using a relatively hydrophobic coupling reagent, dicyclohexylcarbodiimide (DCCD). Since the oligomerization not only required a relatively high concentration of DCCD but also its efficiency was suppressed even at a slightly basic pH of 7.5, another coupling reagent called N-(ethoxycarbonyl)-2-ethoxy-1,2-dihydroquinoline (EEDQ) was examined in order to make use of this technique to access the functional aspects of NACP in vitro by exploring more accurate and reproducible reaction conditions. The EEDQ also gave rise to the NACP oligomerization only in the presence of Abeta25-35 among the variously modified Abeta peptides. The reagent was about three times more effective than DCCD in terms of its optimal concentration to visualize the oligomers. In addition, its oligomerizing potency was not affected by the basic condition. Although physiological and pathological significance of the NACP self-oligomerization are currently unknown, this dramatic phenomenon and its visualization technique could shed light on the determination of molecular relationships of NACP with various intracellular or extracellular biomolecules related to the pathological conditions of Alzheimer's and Parkinson's diseases.

Amyloid beta-Peptides↗
PubMed1997

Nucleotide sequence of the Pseudomonas sp. DJ77 phnG gene encoding 2-hydroxymuconic semialdehyde dehydrogenase.

The nucleotide sequence of a 1520 bp region, spanning the coding region for the meta-cleavage pathway enzyme, 2-hydroxymuconic semialdehyde dehydrogenase, was determined. This enzyme, encoded by the phnG, is the first of three sequential enzymes required for conversion of 2-hydroxymuconic semialdehyde, which is produced from catechol by the PhnE catechol 2,3-dioxygenase, to 2-hydroxypent-2,4-dienoate in the dehydrogenative branch of the pathway. The deduced protein sequence is 484 amino acid residues long with a M(r) of 51504. The phnG has a high degree of homology with genes encoding isofunctional proteins from other Pseudomonas strains. We now show that the relative position of the phnG dehydrogenase gene in the phn operon is unique compared to the other meta-cleavage operons which have a dehydrogenative branch of the pathway.

Alcohol Oxidoreductases↗